28395-03-1 Usage
Description
Bumetanide is a diuretic belonging to the class of benzoic acids, specifically a 4-phenoxybenzoic acid derivative with butylamino and sulfamoyl groups substituted at the hydrogens ortho to the phenoxy group. It is a crystalline solid and is commonly known by the brand name Bumex (Roche). Bumetanide functions by inhibiting the sodium and chloride reabsorption in the ascending limb of the loop of Henle, leading to increased urine output and reduced extracellular fluid volume.
Uses
Used in Pharmaceutical Industry:
Bumetanide is used as an antineoplastic and alkylating agent for the treatment of various types of cancer. It modulates oncological signaling pathways and demonstrates synergistic anticancer effects when combined with conventional chemotherapeutic drugs, enhancing chemo-sensitivity and efficacy in resistant cases.
Used in Cardiology:
Bumetanide is used as a diuretic for relieving edema associated with cardiac insufficiency. It helps in reducing the fluid buildup in the body, which can alleviate the symptoms of congestive heart failure.
Used in Hepatology:
Bumetanide is utilized for the treatment of liver diseases, including conditions that cause edema and ascites. Its diuretic properties help in managing the fluid retention associated with liver dysfunction.
Used in Nephrology:
In the field of kidney diseases, Bumetanide is used for treating conditions like nephrotic syndrome. It aids in reducing the excessive urine output and protein loss in the urine, thus helping in the management of the disease.
Used in Hypertension Management:
Bumetanide is employed as an antihypertensive agent, helping to lower blood pressure by reducing the volume of fluid in the body and decreasing the workload on the heart.
Used in Drug Delivery Systems:
To enhance the efficacy and bioavailability of Bumetanide, various drug delivery systems have been developed. These systems, including organic and metallic nanoparticles, serve as carriers for Bumetanide, aiming to improve its delivery and therapeutic outcomes in different medical applications.
Originator
Burinex,Leo,UK,1973
Manufacturing Process
Preparation of 3-Nitro-4-Phenoxy-5-Sulfamylbenzoic Acid: A mixture of 4-
chloro-3-nitro-5-sulfamylbenzoic acid (140 grams), phenol (100 grams),
sodium hydrogencarbonate (170 grams), and water (1.000 ml) was heated to
85°C while stirring and kept at this temperature for 16 hours. After cooling to
4°C, the precipitated sodium salt of 3-nitro-4-phenoxy-5-sulfamylbenzoic acid
was filtered off and washed with ice water. The sodium salt was dissolved in
boiling water (3,000 ml), and the 3-nitro-4-phenoxy-5-sulfamylbenzoic acid
was precipitated by addition of 4N hydrochloric acid. After cooling, the acid
was isolated by suction and dried. The melting point was 255°-256°C.
Preparation of 3-Amino-4-Phenoxy-5-Sulfamylbenzoic Acid: A suspension of 3-
nitro-4-phenoxy-5-sulfamylbenzoic acid (20 grams) in water (100 ml) was
adjusted to pH 8 by addition of 1N lithium hydroxide. The resulting solution
was hydrogenated at room temperature and 1.1 atmospheres hydrogen
pressure after addition of Pd on carbon catalyst (0.6 grams catalyst containing
10% Pd). After the hydrogen uptake had become negligible, the catalyst was
removed by filtration, and the 3-amino-4-phenoxy-5-sulfamylbenzoic acid was
precipitated from the filtrate by addition of 4N hydrochloric acid to pH 2.5.
After recrystallization from aqueous ethanol and drying, the melting point was
255°-256°C.
Preparation of 3-n-Butylamino-4-Phenoxy-5-Sulfamylbenzoic Acid: To a
suspension of 3-amino-4-phenoxy-5-sulfamyibenzoic acid (10 grams) in nbutanol
(200 ml), concentrated sulfuric acid (2 ml) was added while stirring.
The reaction mixture was heated under reflux under conditions in which the
water formed during the reaction could be removed. When, after dilution with n-butanol, the NMR-spectrum of a sample of the reaction mixture showed at
the two doublets of the aromatic protons in ring A that the butyl-3-amino-4-
phenoxy-5-sulfamylbenzoate formed as an intermediate was more than 90%
converted to the corresponding 3-n-butylaminobenzoate, 2 N sodium
hydroxide (200 ml) was added and the boiling was continued for 45 minutes.
After the saponification, the reaction mixture was neutralized to pH 8 by
addition of concentrated hydrochloric acid.
By cooling, the sodium salt of 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic
acid precipitated. It was filtered off and recrystallized from water (100 ml).
The sodium salt, crystallizing with 3 molecules of water, was then dissolved in
boiling water (200 ml), 1N hydrochloric acid was added to pH 2.5, and after
cooling the precipitated 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid was
collected by filtration. After recrystallization from aqueous ethanol and drying,
the pure compounds were obtained with melting point 230°-231°C.
Therapeutic Function
Diuretic
Biological Activity
Loop diuretic that inhibits the Na + /2Cl - /K + (NKCC) cotransporter. More potent than furosemide (5-(Aminosulfonyl)-4-chloro-2-([2-furanylmethyl]amino)benzoic acid ).
Biochem/physiol Actions
Inhibitor of Na+/K+/Cl- cotransporter.
Clinical Use
A diuretic structurally related to furosemide is bumetanide. This compound also functions as a high-ceiling diuretic in the ascending limb of the loop of Henle. It has a
duration of action of approximately 4 hours. The uses of this compound are similar to those described for furosemide. The dose of bumetanide is 0.5 to 2 mg/day given as
a single dose.
Synthesis
Bumetanide, 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid (21.4.6), is
synthesized from 4-chlorobenzoic acid. In the first stage of synthesis, it undergoes sulfonylchlorination
by chlorosulfonic acid, forming 4-chloro-3-chlorosulfonylbenzoic acid
(21.4.1), which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoic
acid (21.4.2). Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoic
acid (21.4.3), which when reacted with sodium phenolate is transformed into
5-amino-sulfonyl-3-nitro-5-phenoxybenzoid acid (21.4.4). Reduction of the nitro group in
this product by hydrogen using a palladium on carbon catalyst gives 3-amino-5-aminosulfonyl-
5-phenoxybenzoic acid (21.4.5). Finally, reacting this with butyl alcohol in the presence
of sulfuric acid gives the desired bumetanide (21.4.6).
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: increased risk of nephrotoxicity with
NSAIDs; antagonism of diuretic effect with
NSAIDs. Anti-arrhythmics: risk of cardiac toxicity with
anti-arrhythmics if hypokalaemia occurs; effects of
lidocaine and mexiletine antagonised.
Antibacterials: increased risk of ototoxicity with
aminoglycosides, polymyxins and vancomycin; avoid
with lymecycline.
Antidepressants: increased risk of hypokalaemia
with reboxetine; enhanced hypotensive effect with
MAOIs; increased risk of postural hypotension with
tricyclics.
Antiepileptics: increased risk of hyponatraemia with
carbamazepine.
Antifungals: increased risk of hypokalaemia with
amphotericin.
Antihypertensives: enhanced hypotensive effect;
increased risk of first dose hypotensive effect
with alpha-blockers; increased risk of ventricular
arrhythmias with sotalol if hypokalaemia occurs.
Antipsychotics: increased risk of ventricular
arrhythmias with amisulpride or pimozide if
hypokalaemia occurs - avoid with pimozide;
enhanced hypotensive effect with phenothiazines.
Atomoxetine: increased risk of ventricular
arrhythmias if hypokalaemia occurs.
Cardiac glycosides: increased toxicity if hypokalaemia
occurs.
Cytotoxics: increased risk of ventricular arrhythmias
due to hypokalaemia with arsenic trioxide; increased
risk of nephrotoxicity and ototoxicity with platinum
compounds.
Lithium: risk of toxicity.
Metabolism
About 80% of a dose of bumetanide is excreted in the
urine, about 50% as unchanged drug, and 10-20% in the
faeces. No active metabolites are known. In patients with
chronic renal failure the liver takes more importance as an
excretory pathway although the duration of action is not
markedly prolonged.
Check Digit Verification of cas no
The CAS Registry Mumber 28395-03-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,8,3,9 and 5 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 28395-03:
(7*2)+(6*8)+(5*3)+(4*9)+(3*5)+(2*0)+(1*3)=131
131 % 10 = 1
So 28395-03-1 is a valid CAS Registry Number.
InChI:InChI=1/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23)
28395-03-1Relevant articles and documents
Synthetic method of bumetanide
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Paragraph 0015; 0016; 0017; 0018; 0019, (2017/07/20)
The invention provides a synthetic method of bumetanide. The synthetic method comprises the following specific steps: 3-amino-4-phenoxy-5- sulfamoylbenzoic acid and n-butyl alcohol are added to a reactor and stirred at room temperature, a Lewis acid catalyst is added, a reaction is performed for 2-10 h, and pure bumetanide is obtained through post-processing after the reaction. The method is short in reaction step, short in reaction time and high in efficiency, the product yield and purity are higher, reaction conditions are mild, equipment corrosion is avoided, and industrial production is facilitated.
2,3-Dihydrobenzofuran-5-sulfonamide derivatives
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, (2008/06/13)
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Process for the manufacture of substituted amino-benzoic acid derivatives
-
, (2008/06/13)
3-Alkylamino-5-sulfamyl benzoic acid derivatives are prepared by reducing 3-acylamino-5-sulfamyl-benzoic acid derivatives by means of boron hydrides or complex boron hydrides in the presence of Lewis acids.